A TRIGONAL FORM OF THE IDARUBICIN-D(CGATCG) COMPLEX - CRYSTAL AND MOLECULAR-STRUCTURE AT 2.0 ANGSTROM RESOLUTION

The X-ray crystal structure of the complex between the anthracycline i darubicin and d(CGATCG) has been solved by molecular replacement and r efined to a resolution of 2.0 Angstrom. The final R-factor is 0.19 for 3768 reflections with F-o greater than or equal to 2 sigma(F-o). The complex crystallizes in the trigonal space group P3(1) with unit cell parameters a = b = 52.996(4), c = 33.065(2) alpha, alpha = beta = 90 d egrees, gamma = 120 degrees. The asymmetric unit consists of two-duple xes, each one being complexed with two idarubicin drugs intercalated a t the CpG steps, one spermine and 160 water molecules. The molecular p acking underlines major groove-major groove interactions between neigh bouring helices, and an unusually low value of the occupied fraction o f the unit cell due to a targe solvent channel of similar to 30 Angstr om diameter. This is the first trigonal crystal form of a DNA-anthracy cline complex. The structure is compared with the previously reported structure of the same complex crystallizing in a tetragonal form. The geometry of both the double helices and the intercalation site are con served as are the intramolecular interactions despite the different cr ystal forms.